Clinically significant responses achieved with romidepsin across disease compartments in patients with cutaneous T-cell lymphoma

Abstract

Cutaneous T-cell lymphoma (CTCL) is a rare heterogeneous group of non-Hodgkin lymphomas that arises in the skin but can progress to systemic disease (lymph nodes, blood, viscera). Historically, in clinical trials of CTCL there has been little consistency in how responses were defined in each disease “compartment”; some studies only assessed responses in the skin. The histone deacetylase inhibitor romidepsin is approved by the US Food and Drug Administration for the treatment of CTCL in patients who have received at least one prior systemic therapy. Phase II studies that led to approval used rigorous composite end points that incorporated disease assessments in all compartments. The objective of this analysis was to thoroughly examine the activity of romidepsin within each disease compartment in patients with CTCL. Romidepsin was shown to have clinical activity across disease compartments and is suitable for use in patients with CTCL having skin involvement only, erythroderma, lymphadenopathy and/or blood involvement.

The clinical and humanistic burden of cutaneous T-cell lymphomas and response to conventional and novel therapies: results of a systematic review

“…The greatest DOR was reported for acitretin (median DOR: 28.1 months) [77], with the highest PFS seen with brentuximab vedotin (median PFS 15.8, 57.6, and 116.4 months in three studies) [57,61,62]; median PFS with alemtuzumab was 56 months [33]. The median DOR was ≤28 months for other approved therapies [47,[68][69][70][71]73,76,77,[80][81][82], ≤17 months for conventional therapies [59,78] and <12 months for investigational therapies [61][62][63]75,83,84]. Median PFS was ≤13 months for other investigational, approved, and conventional therapies [25,63,64,75,85,86].…”

Romidepsin for the treatment of T-cell lymphomas

“…50 In the trial of Whittaker et al, 49 therapeutic responses were seen at all evaluated disease sites, with a 40% rate of response (38 of 96 patients) among patients with erythroderma or other skin disease, a 35% response rate among those with lymphadenopathy (13 of 37 patients), and a 32% rate of response in those with blood involvement (12 of 37 patients), including 10 of 13 patients with high blood tumor burden. 49,51 Also in this trial, a clinically meaningful reduction in pruritus (CMRP) was seen in 43% of patients (28 of 65) who had at least moderate pruritus at baseline, including 10 of 24 patients (42%) who had blood involvement, 52 months, while median PFS was 29 months for patients with a confirmed or unconfirmed CR. 53 In the study by Piekarz et al, 40 the median TTP was 13.0 months for patients with a CR or PR, 4.6 months for patients with stable disease, or 1.4 months for patients with disease progression.…”

Pruritus Reduction with Systemic Anti-lymphoma Treatments in Patients with Cutaneous T Cell Lymphoma: A Narrative Review

“…However, CMRP also occurred in nonresponders (11/39, 28%)—all with best response of stable disease (SD). Patients were also able to achieve CMRP irrespective of disease compartment involvement; although lymphadenopathy significantly lowered rates of CMRP, erythroderma, blood involvement, and higher blood tumour burden (surrogate for SS) did not [58]. …”

“…The definition of complete resolution was more stringent in the study with romidepsin, requiring VAS = 0 for ≥8 vs ≥4 consecutive weeks [56, 71]. Subanalyses of the romidepsin study also showed that patients experienced pruritus reduction irrespective of disease compartment involvement, and in difficult-to-treat populations including patients with cutaneous tumours, folliculotropic MF, and those with prior chemotherapies [58–60]. Importantly, vorinostat trials allowed the use of concomitant anti-pruritic medications, which could impact results, whereas the romidepsin trial did not [56, 71, 72].…”